1. Field of the Invention
This invention relates to the field of medical devices, especially drug delivery devices such as drug eluting vascular stents.
2. Description of the State of the Art
A stent is a tubular scaffolding structure used to mechanically uphold the patency of the lumen in which the stent is placed. Stents are being modified to also provide pharmacological therapy. One method of medicating a stent is with the use of a polymer coating impregnated with a drug. A variety of polymers can be used to coat stents. Of particular interest is a copolymer of ethylene and vinyl alcohol, also known as poly(ethylene-co-vinyl alcohol) having a general formula —[CH2—CH2]m—[CH2—CH(OH)]n—. Poly(ethylene-co-vinyl alcohol) is also known under the trade name EVAL and is distributed commercially by Aldrich Chemical Company of Milwaukee, Wis. EVAL is also manufactured by EVAL Company of America of Lisle, Ill.
EVAL possesses a desirable impermeability to oxygen, is biologically compatible, and adheres well to metals, such as stainless steel. At the same time, the biological compatibility of EVAL can be improved. One way to improve the biological compatibility of EVAL can be by forming an adduct of EVAL with a compound that can provide enhanced biological compatibility. Such highly biologically compatible compounds include poly(alkylene glycols) one example of which is poly(ethylene glycol)(PEG). For example, EVAL can be derivatized by having PEG conjugated to EVAL to form an EVAL-PEG adduct. The EVAL-PEG adduct is expected to have improved biological compatibility, for example, to have non-fouling properties. The term “non-fouling property” refers to the ability of the stent surface to prevent or at least reduce a build-up of a thick, denatured layer of protein which typically tends to accumulate on the surface of a bare metal stent or a stent coated with polymers such as EVAL. Such accumulation or “fouling” of the stent surface is a result of the body's reaction to a foreign material. The fouling of the stent surface is undesirable for long-term tissue compatibility.
While PEG-modified EVAL is expected to have improved biological compatibility including non-fouling property, some further improvements are desirable. In particular, PEG can disappear quickly from the EVAL-PEG adduct as a result of hydrolysis, if PEG is attached to EVAL via hydrolytically unstable links such as anhydride, ester, orthoester or acetal bonds. As a result, the duration of service of the EVAL-PEG based coating can be less than optimal.
In view of the foregoing, it is desirable to have hydrolytically stable biologically compatible derivatives of EVAL having non-fouling properties. The present invention provides such derivatives.